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J. Biol. Chem., Vol. 282, Issue 51, 36923-36932, December 21, 2007

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Gp120 V3-dependent Impairment of R5 HIV-1 Infectivity Due to Virion-incorporated CCR5^*

Kazuaki Monde, Yosuke Maeda, Yuetsu Tanaka, Shinji Harada, and Keisuke Yusa¹

From the Department of Medical Virology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan and the Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 903-0215, Japan

Entry of R5 human immunodeficiency virus type 1 (HIV-1) into target cells requires sequential interactions of the envelope glycoprotein gp120 with the receptor CD4 and the coreceptor CCR5. We investigated replication of 45 R5 viral clones derived from the HIV-1_JR-FLan library carrying 0–10 random amino acid substitutions in the gp120 V3 loop. It was found that 6.7% (3/45) of the viruses revealed 10-fold replication suppression in PM1/CCR5 cells expressing high levels of CCR5 compared with PM1 cells expressing low levels of CCR5. In HIV-1_V3L#08, suppression of replication was not associated with entry events and viral production but with a marked decrease in infectivity of nascent progeny virus. HIV-1_V3L#08, generated from infected PM1/CCR5 cells, was 98% immunoprecipitated by anti-CCR5 monoclonal antibody T21/8, whereas the other infectious viruses were only partially precipitated, suggesting that incorporation of larger amounts of CCR5 into the virions caused impairment of viral infectivity in HIV-1_V3L#08. The results demonstrate the implications of an alternative influence of CCR5 on HIV-1 replication.

Received for publication, June 28, 2007 , and in revised form, October 11, 2007.

^* This work was supported by grants from the Ministry of Education, Science, Sports, and Culture and the Ministry of Health Labor and Welfare, Japan, and in part by the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Re-emerging Infectious (Renkei Jigyo: no. 78, Kumamoto University). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-96-373-5130; Fax: 81-96-373-5132; E-mail: yusak{at}kumamoto-u.ac.jp.

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